Recombinant cytomegalovirus vaccine

Abstract

The present invention provides a non-defective adenovirus recombinant expression system for the expression of the HCMV gB subunit, an immunogenic fragment of the gB subunit, and for the expression of non-structural immediate-early exon 4 proteins, said recombinant HCMV-expressing adenovirus being useful as a vaccine.

What is claimed is: 
     
       1. A non-defective recombinant adenovirus containing a fragment of the gB gene selected from the group consisting of (a) the gB gene fragment encoding amino acid 1 to amino acid 700 of human cytomegalovirus gB subunit protein SEQ ID NO:2 and (b) smaller fragments thereof, said smaller fragments comprising the gB gene fragment encoding amino acid 155 to 303 of human cytomegalovirus gB subunit protein SEQ ID NO:2, said gB gene fragment being under the control of an expression control sequence, said adenovirus capable of expressing said subunit protein fragment. 
     
     
       2. The non-defective recombinant adenovirus according to claim 1 wherein the fragment of the gB gene encodes amino acid 1 to amino acid 303 of human cytomegalovirus gB subunit protein SEQ ID NO:2. 
     
     
       3. The non-defective recombinant adenovirus according to claim 2 wherein the fragment of the gB gene encodes amino acid 1 to amino acid 465 of human cytomegalovirus gB subunit protein SEQ ID NO:2. 
     
     
       4. The non-defective recombinant adenovirus according to claim 1 wherein the fragment of the gB gene encodes amino acid 155 to amino acid 303 of human cytomegalovirus gB SEQ ID NO:2. 
     
     
       5. The non-defective recombinant adenovirus according to claim 1 wherein the fragment of the gB gene encodes amino acid 1 to amino acid 700 of human cytomegalovirus gB SEQ ID NO:2. 
     
     
       6. A cytomegalovirus immunogenic composition comprising a non-defective recombinant adenovirus and suitable pharmaceutical carrier, wherein said recombinant adenovirus contains a fragment of the gB gene selected from the group consisting of (a) the gB gene fragment encoding amino acid 1 to amino acid 700 of human cytomegalovirus gB subunit protein SEQ ID NO:2 and (b) smaller fragments thereof, said smaller fragments comprising the gB gene fragment encoding amino acid 155 to amino acid 303 of human cytomegalovirus gB subunit protein SEQ ID NO:2, said gene fragment being under the control of an expression control sequence, said adenovirus capable of expressing said subunit protein fragment. 
     
     
       7. The immunogenic composition according to claim 6 wherein said adenovirus is selected from the group consisting of an adenovirus type 5, adenovirus type 4 and adenovirus type 7 strain. 
     
     
       8. The immunogenic composition according to claim 7 wherein said gB subunit fragment is obtained from the Towne strain cytomegalovirus, and the adenovirus is type 5. 
     
     
       9. The cytomegalovirus immunogenic composition according to claim 6 wherein the fragment of the gB gene encodes amino acid 1 to amino acid 303 of human cytomegalovirus gB subunit protein SEQ ID NO:2. 
     
     
       10. The cytomegalovirus immunogenic composition according to claim 6 wherein the fragment of the gB gene encodes amino acid 1 to amino acid 465 of human cytomegalovirus gB subunit protein SEQ ID NO:2. 
     
     
       11. The cytomegalovirus immunogenic composition according to claim 6 wherein the fragment of the gB gene encodes amino acid 155 to amino acid 303 of human cytomegalovirus gB subunit protein SEQ ID NO:2. 
     
     
       12. The cytomegalovirus immunogenic composition according to claim 6 wherein the fragment of the gB gene encodes amino acid 1 to amino acid 700 of human cytomegalovirus gB subunit protein SEQ ID NO:2. 
     
     
       13. A method for eliciting an immune response against human cytomegalovirus in an animal comprising administering an effective amount of a cytomegalovirus immunogenic composition comprising a non-defective recombinant adenovirus and suitable pharmaceutical carrier, wherein said recombinant adenovirus contains a fragment of the gB gene selected from the group consisting of (a) the gB gene fragment encoding amino acid 1 to amino acid 700 of human cytomegalovirus gB subunit protein SEQ ID NO:2 and (b) smaller fragments thereof, said smaller fragments comprising the gB gene fragment encoding amino acid 155 to amino acid 303 of human cytomegalovirus gB subunit protein SEQ ID NO:2, said gene fragment being under the control of an expression control sequence, said adenovirus capable of expressing said subunit protein fragment. 
     
     
       14. The method according to claim 13 comprising orally administering said immunogenic composition. 
     
     
       15. The method according to claim 13 wherein an effective amount is 10 5  to 10 8  plaque forming units. 
     
     
       16. The method according to claim 13 wherein the fragment of the gB gene encodes amino acid 1 to amino acid 303 of human cytomegalovirus gB subunit protein SEQ ID NO:2. 
     
     
       17. The method according to claim 13 wherein the fragment of the gB gene encodes amino acid 1 to amino acid 465 of human cytomegalovirus gB subunit protein SEQ ID NO:2. 
     
     
       18. The method according to claim 13 wherein the fragment of the gB gene encodes amino acid 1 to amino acid 700 of human cytomegalovirus gB subunit protein SEQ ID NO:2. 
     
     
       19. The method according to claim 13 wherein the fragment of the gB gene encodes amino acid 155 to amino acid 303 of human cytomegalovirus gB subunit protein SEQ ID NO:2.